2025 Volume 72 Issue 5 Pages 475-485
Limited real-world data are available on persistence to growth hormone replacement therapy (GHRT) in Japan. Therefore, we used the Japan Medical Data Center claims database to retrospectively investigate persistence with GHRT in patients with pediatric growth hormone deficiency (pGHD). We identified 1,020 patients with pGHD treated with GHRT. The mean age at initial diagnosis was 7.5 ± 3.8 years, and we found a bimodal pattern in age, with peaks at 3 and 12 to 13 years of age; the peaks were more pronounced in male patients. After excluding patients with early withdrawal, 1,016 patients were eligible for persistence analysis. The time to initial treatment discontinuation, i.e., the first prescription-free period of 182 days (6 months) or more, for 50% of the patients was 2,526 days, which was similar to that of treatment completion (2,626 days). Most patients persisted with GHRT until they completed treatment, but 24 out of 1,016 (2.4%) had a treatment discontinuation. The mean proportion of days covered was 89.8%. Being female (hazard ratio [95% CI]: 1.85 [1.36–2.51]) and older age at diagnosis (1.50 [1.41–1.60]) were associated with shorter time to discontinuation. This finding suggests that most patients persist with GHRT until puberty. In conclusion, although most Japanese patients with pGHD appear to persist well with GHRT, some complete GHRT before puberty. Additionally, there are patients diagnosed and starting treatment just before puberty. Therefore, continued efforts towards early referral and diagnosis are important.
Short stature can be identified by comparing height to a standardized growth chart, and a child is generally classified as having short stature if their height is more than 2 standard deviations below the mean in children with the same age and sex [1]. One of the pathological causes of short stature is growth hormone deficiency (GHD).
In children, pediatric GHD (pGHD) leads to slowed height velocity and a shorter adult height compared with the target height range [2]. This disorder can negatively impact a child’s quality of life, influence their social and emotional well-being, and result in abdominal obesity, reduced lean body mass, decreased bone mass, fatigue, and impaired psychosocial function in adulthood [3-5].
Diagnosis of pGHD requires provocative tests of GH secretion (GH stimulation tests); several types of stimuli are available, including arginine and glucagon. The estimated prevalence of pGHD varies widely, from 1 in 3,500 to 1 in 10,000, depending on the cut-off criteria used for the GH stimulation test [6-8]. In Japan, the prevalence of pGHD per 10,000 children is reported to be 2.14 for boys and 0.71 for girls [9].
In most cases, growth hormone replacement therapy (GHRT) can help children catch up with normal growth and achieve adult height within the target height range [2]. However, not all children with pGHD treated with GHRT reach their target height range, partially due to poor treatment adherence [10, 11]. A real-world database study and systematic reviews of previous studies reported that GHRT non-adherence rates among children with pGHD ranged from 4.7% to 71%, indicating that challenges to adherence exist [12-14]. In addition, patients with early diagnosed pGHD are reported to be much more responsive to GHRT than those diagnosed at an older age, so early detection and treatment of pGHD are important and considered a cost-effective strategy [15, 16]. Moreover, the continuation of treatment is also a crucial factor in achieving optimal height outcomes. A US study of children with pGHD reported that those with better treatment persistence until reaching their final height showed higher average height standard deviation scores compared to those who discontinued for any reason [17]. In a UK retrospective study, high levels of treatment discontinuation were observed in pGHD, despite very high levels of early persistence [18].
In Japan, there have been longstanding efforts to raise awareness about early referral to an endocrinologist, early diagnosis, and sustained treatment for children with pGHD. However, the current trends regarding age at diagnosis and treatment continuation have not been fully elucidated. Therefore, the aim of this study was to estimate the persistence to GHRT in Japanese patients with pGHD. The study also explored the proportion of days covered (PDC)—as a surrogate measure of treatment adherence—and patient demographics and clinical characteristics.
This was a retrospective cohort study in a real-world setting that used data from the Japan Medical Data Center (JMDC) claims database (JMDC Inc., Tokyo, Japan) collected between January 2005 and June 2021. In 2020, the JMDC claims database contained around 9.8 million identifiers [19]. The JMDC claims database contains anonymized data on all claims of employees and their family members from health insurance associations. Therefore, patients can be tracked across hospitals, unless they leave their health insurance association, e.g., because they change jobs.
This study was approved by the MINS Research Ethics Committee (approval number: MINS-REC-220223; date of approval: September 8, 2022).
Patient IdentificationEligible patients were those diagnosed with pGHD between January 2005 and June 2021; pGHD was defined by the disease codes used in the JMDC claims database (Supplementary Table 1). The date of first diagnosis of pGHD was defined as the index date. The observation period of patients is defined as the duration from the index date and the date of their last claim in the database. Patients must also have undergone a GH stimulation test and received GHRT. A GH stimulation test was defined by the procedure codes of the JMDC claims database, and GHRT was defined by the World Health Organization Anatomical Therapeutic Chemical code (H01AC).
The Japanese guideline for pGHD [20] stipulates that patients should be diagnosed with pGHD when their results of two or more GH stimulation tests are abnormal. If all results of GH stimulation tests are abnormal, the severity of pGHD is classified as moderate or severe on the basis of the maximum peak GH level. On the other hand, if there is one normal result, the severity is classified as mild. Mild pGHD is an indication for GH in Japan although it is classified as non-GHD in many other countries. Unfortunately, due to the lack of the results of the GH stimulation tests in the claims database, we were unable to clearly distinguish the severity of GHD. Therefore, patients who underwent three or more GH stimulation tests were excluded given that majority of them would be diagnosed as mild GHD.
For the inclusion criteria regarding the age of eligible patients, we referred to a bone age of at least 17 years for boys and 15 years for girls, which is one of the criteria for determining that there is no indication for continued treatment with GH, according to the “Pediatric Growth Hormone Therapy Indication Determination” of the Foundation of Growth Science [21]. Although there is no information on bone age in this database, we used this as a reference and included patients whose age on the index date was less than 17 years for boys and less than 15 years for girls. To ensure that we selected patients first diagnosed with pGHD during the observation period, eligible patients were required to have available medical records for at least 12 months before and 3 months after the index date.
OutcomesThe outcomes were persistence to GHRT and the PDC. Persistence was defined as the proportion of patients who had not yet discontinued GHRT by a given day after treatment initiation. The follow-up period for the persistence analysis was defined as the period from the index date to earlier of the date of the last claim or the date of the termination of GHRT because of our definition of pGHD using the criteria for termination of GHRT. Therefore, for boys who became 17 years old and girls who became 15 years old during the observation period, the follow-up period was defined as from the index date to the 15th or 17th birthday.
PDC was defined as the number of days covered by GHRT divided by the number of days in the follow-up period, which is a surrogate outcome of treatment adherence. Treatment discontinuation was defined as the first prescription-free period of 182 days (6 months) or more in the follow-up period because the usual prescription interval in Japanese clinical practices is a month or a few months at the most, and physicians would not pause treatment for 6 months or more. We also explored persistence defined as the proportion of patients who did not complete treatment because patients could resume GHRT after discontinuing treatment for a while; to confirm that GHRT was terminated, treatment completion was defined as an observable period of 182 days (6 months) or more after the last prescription of GH. As treatment completion was defined irrespective of the age of patients, a histogram of age at completion was examined in order to investigate patients who quitted GHRT long before the onset of puberty.
Statistical analysisContinuous variables were reported as the mean, standard deviation, median, and interquartile ranges with minimum and maximum values, depending on the data distribution. Categorical variables were summarized as frequencies and percentages of the study population.
To estimate the prevalence of pGHD in the Japanese general population, we estimated the prevalence in the JMDC claims database in 2020 and adjusted it for age and sex using data from the latest national census in 2020 [22].
We investigated the persistence of GHRT with Kaplan-Meier curves and proportional hazards models. Persistence was visualized with a Kaplan-Meier plot and factors affecting persistence were estimated with a Cox proportional hazard model. Patients who discontinued or were censored at first GH treatment were excluded from the persistence analysis as early withdrawals. Besides age at diagnosis and sex, we added use of pituitary hormone treatment other than GHRT as a covariate in the Cox proportional hazard model because patients with severe pGHD tend to receive multiple hormone replacements. As additional covariates, we added the mean number of concomitant drugs other than hormone treatment and the mean cost of treatments in the past 12 months before the start of GHRT (to examine whether economic or drug management burdens affect persistence to GHRT) and information on whether patients attended a facility with more than the median number of patients per facility (to explore the effect of facility experience on the persistence). If the proportional hazard assumption was not met, persistence was also visualized with a stratified Kaplan-Meier plot. As a sensitivity analysis, we analyzed persistence defined as the proportion of patients without completion of GHRT rather than discontinuation of GHRT.
The JMDC claims database specifies the amount of GH prescribed but does not include information on the exact daily dose and number of days of GH prescription because weight is not recorded. Therefore, for PDC we assumed that GH was prescribed until the next prescription as long as the prescription interval was less than 182 days; if the interval was 182 days or more, we assumed that the patient had stopped GHRT at the date of the prescription just before the start of the prescription interval.
We conducted the main analysis in order to align with the definitions of GHD in global diagnostic criteria and excluded patients who underwent three or more GH stimulation tests. Additionally, we performed a sensitivity analysis that included patients who had experienced three or more GH stimulation tests in order to comply with the Japanese guideline.
All statistical analyses were performed with R (version 4.2.1, R Foundation, Vienna, Austria). Statistical significance was considered at a two-sided p value of less than 0.05.
We identified 1,020 eligible patients with GHD. Their background information is summarized in Table 1. Female patients accounted for just over a third of the total sample and had a slightly lower mean age at initial diagnosis than male patients. A small percentage of patients had a history of any tumor and had received pituitary hormone replacement other than GH.
| All | Male | Female | |
|---|---|---|---|
| N (%) | 1,020 (100.0%) | 647 (63.4%) | 373 (36.6%) |
| Age at diagnosis, mean ± SD, (year) | 7.5 ± 3.8 | 8.0 ± 3.9 | 6.7 ± 3.4 |
| Age at first GH administration, mean ± SD, (year) | 7.8 ± 3.7 | 8.2 ± 3.8 | 7.1 ± 3.3 |
| Time from diagnosis to first GH administration, median [IQR], (day) | 40 [98] | 38 [85.5] | 47 [124] |
| Number of GH stimulation tests, n (%) | |||
| 1 | 270 (26.5%) | 160 (24.7%) | 110 (29.5%) |
| 2 | 750 (73.5%) | 487 (75.3%) | 263 (70.5%) |
| Any tumor a, n (%) | 27 (2.6%) | 15 (2.3%) | 12 (3.2%) |
| Pituitary hormones b, n (%) | 54 (5.3%) | 30 (4.6%) | 24 (6.4%) |
| Concomitant medications c, mean ± SD, n | 3.0 ± 2.5 | 3.0 ± 2.6 | 2.9 ± 2.4 |
| Medical costs d, median [IQR], (JPY) | 37332.5 [20981.7] | 37678.3 [20504.2] | 37678.3 [21268.3] |
| Patients per facility, at first GH administration, median [IQR], n | 9 [17] | 9 [17] | 8 [21] |
a Number of patients who experienced any tumor
b Number of patients who used pituitary hormones other than growth hormone before first growth hormone administration
c Mean number of concomitant medications other than pituitary hormones per month in the 12 months before first growth hormone administration
d Mean medical costs other than pituitary hormones per month in the 12 months before first growth hormone administration (Japanese Yen/month)
GH, growth hormone
A histogram of age at diagnosis is shown in Fig. 1. There was a bimodal pattern in age, with peaks at 3 and 12 to 13 years of age, whereby the peaks were more pronounced in male patients. The peak at 3 years was seen in 106/647 (16.4%) male patients and 61/373 (16.4%) female ones. The second peak was earlier in female patients. The longitudinal trend of age at diagnosis is shown in Table 2.
| Year of diagnosis | 2006 | 2007 | 2008 | 2009 | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All | Number of patients | 4 | 2 | 5 | 12 | 19 | 29 | 37 | 36 | 72 | 74 | 98 | 133 | 161 | 176 | 147 | 15 |
| Mean (age) | 10.5 | 4.0 | 9.2 | 8.7 | 7.6 | 7.1 | 7.5 | 8.1 | 7.7 | 7.9 | 6.5 | 7.7 | 7.6 | 7.3 | 7.6 | 8.2 | |
| Median (age) | 11.0 | 4.0 | 8.0 | 8.5 | 8.0 | 6.0 | 8.0 | 9.0 | 8.0 | 8.0 | 5.0 | 7.0 | 8.0 | 7.0 | 7.0 | 9.0 | |
| Female | Number of patients | 3 | 0 | 3 | 2 | 5 | 7 | 14 | 10 | 24 | 27 | 40 | 48 | 55 | 70 | 59 | 6 |
| Mean (age) | 10.3 | 0.0 | 8.0 | 5.0 | 6.0 | 8.4 | 6.4 | 6.5 | 6.8 | 7.3 | 6.0 | 6.8 | 6.5 | 6.7 | 6.8 | 8.0 | |
| Median (age) | 11.0 | 0.0 | 7.0 | 5.0 | 7.0 | 11.0 | 6.0 | 5.0 | 6.5 | 7.0 | 4.0 | 6.0 | 6.0 | 6.0 | 7.0 | 9.0 | |
| Male | Number of patients | 1 | 2 | 2 | 10 | 14 | 22 | 23 | 26 | 48 | 47 | 58 | 85 | 106 | 106 | 88 | 9 |
| Mean (age) | 11.0 | 4.0 | 11.0 | 9.4 | 8.1 | 6.7 | 8.2 | 8.7 | 8.2 | 8.3 | 6.9 | 8.3 | 8.2 | 7.6 | 8.1 | 8.3 | |
| Median (age) | 11.0 | 4.0 | 11.0 | 9.5 | 9.0 | 5.0 | 9.0 | 10.0 | 8.5 | 9.0 | 5.5 | 8.0 | 9.0 | 8.0 | 8.0 | 10.0 |
Comorbidities at diagnosis are summarized in Table 3. The most frequent comorbidities were hypothyroidism and hypopituitarism.
| Comorbidities (N = 1,607) | n | (%) |
|---|---|---|
| Hypothyroidism | 101 | 9.9% |
| Hypopituitarism | 46 | 4.5% |
| Attention deficit hyperactivity disorder | 22 | 2.2% |
| Hypogonadism | 19 | 1.9% |
| Hypoadrenalism | 13 | 1.3% |
| Brain tumors | 13 | 1.3% |
| Renal diseases | 12 | 1.2% |
| Central enuresis | 9 | 0.9% |
| Scoliosis | 8 | 0.8% |
| Neonatal asphyxia | 8 | 0.8% |
| Silver-Russell syndrome | 3 | 0.3% |
| Obesity | 3 | 0.3% |
| Congenital heart disease | 2 | 0.2% |
| Encephalitis | 2 | 0.2% |
| Encephalopathy | 2 | 0.2% |
| Type 2 diabetes | 1 | 0.1% |
We identified 931 pGHD patients in 2020. The adjusted prevalence was 63.96 (95% CI, 62.28–65.63) per 100,000 for male and 43.23 (95% CI, 41.72–44.74) for female as estimated by extrapolation using data from the national census 2020.
PersistenceThe Kaplan-Meier plot of persistence is shown in Fig. 2. After excluding patients with early withdrawal, 1,016 out of 1,020 patients were eligible for the persistence analysis. The time to treatment discontinuation for 50% of the patients was about 7.1 years (2,581 days) for boys and 7.0 years (2,526 days) for girls (p = 0.84, Fig. 2a). In the sensitivity analysis, time to completion for 50% of the patients was 7.2 years (2,626 days) for boys and 7.0 years (2,526 days) for girls (p = 0.90, Fig. 2b). Out of 1,016 patients, 24 (2.4%) experienced a treatment discontinuation, of whom 17 (70.8%) discontinued GHRT only once. A total of 187 (18.4%) patients completed their treatment, and a histogram of the age at treatment completion is presented in Fig. 3. Especially, 16 (8.6%) of 187 who completed GHRT quitted aged less than 10, long before the age specified in the Japanese guideline as the termination criterion. On the other hand, out of 1,016 eligible patients, 54 (5.3%) patients were censored because they reached the age of termination.
GHD, growth hormone deficiency; GHRT, growth hormone replacement therapy
We used Cox regression to explore factors affecting persistence to GHRT (Fig. 4a) and found that being female (HR [95% CI], 1.85 [1.36–2.51]) and older age at diagnosis (1.50 [1.41–1.60]) were significant risk factors for treatment discontinuation. Patients receiving pituitary hormone replacement other than GH tended to have a longer time to discontinuation (0.68 [0.31–1.52]), although the difference was not significant. The risk factors for treatment completion were found to be similar to those for treatment discontinuation (Fig. 4b). GHRT was continued until reaching the termination condition by significantly more patients treated with pituitary hormones other than GH (7/52; 13.5%) than by patients not treated with pituitary hormones (47/964; 4.9%). The results of the stratified Kaplan-Meier plots are shown in Supplementary Figs. 1–4.
a: More than the median number of patients per facility
b: Mean cost of treatments in the past 12 months before the start of GHRT
c: Mean number of concomitant drugs other than hormone treatment in the past 12 months before the start of GHRT
d: Use of pituitary hormones other than growth hormones before the index date
The mean PDC was 89.8%, and the median [IQR] was 100.0% [0.0%]. The proportion of patients without discontinuation was 95.4% (973/1,020).
Sensitivity Analysis Including Patients with Three or More GH Stimulation TestsWe performed a sensitivity analysis including patients who underwent three or more GH stimulation tests and would have been diagnosed with mild GHD in Japanese guideline, and identified 1,607 patients. The number of patients who underwent three or more GH stimulation test was 587 (36.5%) and the characteristics of included patients were similar to those of the overall population (Supplementary Table 2), although the median of six patients per facility was slightly lower than that in the main analysis. The estimated prevalence in 2020 was 100.38 (95% CI, 98.28–102.47) per 100,000 for male, and 66.57 (95% CI, 64.70–68.45) for female. The Kaplan-Meier plot of persistence was also similar to that of the overall population (Supplementary Fig. 5). The mean PDC was 90.1%, and the median [IQR] was 100.0% [0.0%]. The proportion of patients without discontinuation was 96.0% (1,543/1,607).
This retrospective database study examined the persistence of GHRT in patients with pGHD.
In this study, the estimated prevalence of pGHD was 54.55 per 100,000 (63.96 for boys and 43.23 for girls) in 2020, which is comparable to that reported by Tanaka et al., who found a prevalence of 55.2 per 100,000 (72.2 for boys and 37.1 for girls) in a Japanese registry [23]. In sensitivity analysis including mild GHD in Japanese guideline, the prevalence increased to 85.04 per 100,000 (100.38 for boys and 66.57 for girls). Our results are in line with the result of the Japanese registry of the Foundation for Growth Science [24] that showed there is an increasing number of cases with mild GHD.
The mean age at initial diagnosis was 7.5 ± 3.8 years, which was earlier than the 9.1 ± 3.4 years reported in a previous study [25]. That study found a similar bimodal pattern of age at diagnosis [25]. The second peak was earlier in female patients and is thought to be related to puberty (e.g., early puberty, last-chance treatment). Raising awareness of the importance of early diagnosis and treatment among general pediatricians, school nurses, and others who may encounter children with short stature should be continued because it would be preferable to diagnose patients earlier than shortly before puberty.
The mean PDC was 89.8%, which was much higher than that in a previous database study in the US (49%) [12]. Unlike patients in the US, Japanese patients with pGHD may have been able to avoid discontinuing GHRT for financial reasons because Japan provides universal health insurance and subsidized pediatric care; these factors may also have contributed to the high persistence to GHRT and high PDC in our study. The Kaplan-Meier curve showed similar results for treatment discontinuation and treatment completion. The proportion of patients who experienced a prescription-free period of 6 months or more before treatment completion was 2.4%. The reasons for such prescription-free periods were unknown because they were not recorded in the database.
Our results suggest that most of them persist to GHRT until treatment completion. However, persistence and PDC may have been overestimated because we defined treatment discontinuation as a prescription-free period of more than 6 months (182 days), which is longer than the 60-day period used in previous studies [12]. Nevertheless, we believe that our criterion of 6 months is appropriate because a prescription interval of a few months (but fewer than 6 months) is common in Japanese clinical practices.
Because most patients with pGHD in Japan appear to continue GHRT until puberty, it is not surprising that Cox regression identified age as a significant factor for shorter treatment duration. In addition, being female also significantly affected persistence to GHRT. The possible reason may be that girls enter puberty earlier than boys [26]. Fifty-five patients had continued GHRT beyond the age of termination defined by the Japanese guideline (17th birthday for boys, 15th birthday for girls), indicating that some of these patients may have had child-onset adult GHD.
Although our result showed the persistence to GHRT in patients with pGHD was quite favorable, there were patients who discontinued GHRT long before reaching the age of termination defined by the Japanese guideline (i.e., 17 years old for boys and 15 years old for girls) as shown in Fig. 3. Daily injectable formulations have been reported to be burdensome for patients [27, 28] and to affect adherence [29, 30], so new treatment options such as long-acting GH formulations that would be expected to reduce treatment burden [31] may help to maintain adherence to GHRT. In addition, health care providers need to provide adequate support and education on the importance of continuing therapy to help patients maintain the benefits provided by GHRT.
Because the JMDC claims database provides data from claims, some data were missing. For example, it had no information on the reason for discontinuation or completion of treatment. Some patients with GHD may have been misclassified because they were identified with disease codes, as is commonly performed in database studies. The database may not capture all data for reasons such as omission of claims or recording errors. We cannot rule out that our results may not fully reflect real-world clinical settings. The JMDC claims database includes data from an employed, primarily working-age population and their families, but may not be representative of the general population because such people may have a greater knowledge and understanding of the disease and its treatment. Additionally, it has only limited information on self-employed patients and their families and does not include data from private practices (i.e., data for treatment not covered by insurance).
The PDC is often used as a surrogate measure of adherence because it provides information on whether a prescribed medication was available to a patient. However, PDC may be overestimated when using prescription records from a claims database because such databases do not record whether patients actually used their prescribed products appropriately. In addition to the limitations of the PDC itself, there are limitations related to the PDC estimated in this study: although we assumed that a patient stopped injecting GHRT just before any prescription interval of 182 days or more, patients were expected to use somatropin after the last prescription. This limitation may have resulted in the PDC being underestimated.
Lastly, because Japan has both a Medical Aid Program for Chronic Pediatric Diseases of Specified Categories and a universal health insurance system, the results of this study cannot be easily extrapolated to other countries.
The authors would like to thank Hiroki Murayama of Novo Nordisk Pharm Ltd. for valuable discussions. The authors were supported by Tatsuhiro Uenishi and Kaori Endo of Medilead, Inc. as a contracted research organization.
All authors contributed to the study conception and interpretation of analysis. All authors critically reviewed the manuscript and approved it. They also agreed to be accountable for the accuracy and integrity of this manuscript.
JM reports funding from Novo Nordisk Pharma Ltd. and also received honoraria from Novo Nordisk Pharma Ltd., Pfizer Japan Inc., and JCR Pharmaceuticals Co., Ltd. YS and ST are employees and own stock of Novo Nordisk Pharma Ltd. SD is a member of the advisory boards of Novo Nordisk Pharma Ltd. and Pfizer Japan Inc. and reports honoraria from Novo Nordisk Pharma Ltd., Pfizer Japan Inc., JCR Pharmaceuticals Co., Ltd., and Sandoz Pharma K.K.
| ICD10 codes | Disease code | Disease name |
|---|---|---|
| E230 | 8835937 | Isolated growth hormone deficiency |
| E230 | 8842944 | Growth hormone deficiency dwarfism |
| E230 | 8844069 | Growth hormone hyposecretion |
| All | Male | Female | |
|---|---|---|---|
| N (%) | 1,607 (100.0%) | 1,012 (63.0%) | 595 (37.0%) |
| Age at diagnosis, mean ± SD, (year) | 7.8 ± 3.7 | 8.2 ± 3.9 | 7.0 ± 3.3 |
| Age at first GH administration, mean ± SD, (year) | 8.1 ± 3.6 | 8.6 ± 3.8 | 7.4 ± 3.3 |
| Time from diagnosis to first GH administration, median [IQR], (day) | 39 [110] | 36 [102] | 47 [136] |
| Number of GH stimulation tests, n (%) | |||
| 1 | 270 (16.8%) | 160 (15.8%) | 110 (18.5%) |
| 2 | 750 (46.7%) | 487 (48.0%) | 263 (44.2%) |
| 3 or more | 587 (36.5%) | 365 (36.1%) | 222 (37.3%) |
| Any tumor a, n (%) | 38 (2.4%) | 25 (2.5%) | 13 (2.2%) |
| Pituitary hormones b, n (%) | 85 (5.3%) | 51 (5.0%) | 34 (5.7%) |
| Concomitant medications c, mean ± SD, n | 3.0 ± 2.5 | 3.1 ± 2.5 | 3.0 ± 2.4 |
| Medical costs d, median [IQR], (JPY) | 37945.0 [22004.6] | 38620.8 [21360.4] | 36998.3 [22420.6] |
| Patients per facility, at first GH administration, median [IQR], n | 6 [10] | 6 [9] | 5 [10.5] |
a Number of patients who experienced any tumor
b Number of patients who used pituitary hormones other than growth hormone before first growth hormone administration
c Mean number of concomitant medications other than pituitary hormones per month in the 12 months before first growth hormone administration
d Mean medical costs other than pituitary hormones per month in the 12 months before first growth hormone administration (Japanese Yen/month)
GH, growth hormone
GHD, growth hormone deficiency; GHRT, growth hormone replacement therapy
GHD, growth hormone deficiency; GHRT, growth hormone replacement therapy
GHD, growth hormone deficiency; GHRT, growth hormone replacement therapy
GHD, growth hormone deficiency; GHRT, growth hormone replacement therapy
